Introduction

Uses for Pertuzumab

Breast Cancer

In combination with trastuzumab and docetaxel for the treatment of metastatic breast cancer in patients whose tumors overexpress the HER2 protein and who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.1

Efficacy established based on progression-free survival; effect on overall survival not established.12

Pertuzumab Dosage and Administration

General

Because of risk of infusion or hypersensitivity reactions, closely observe patients for 60 minutes after first infusion and for 30 minutes after subsequent infusions.1 (See Infusion or Hypersensitivity Reactions under Cautions.)

Consult specialized references for procedures for proper handling (e.g., use of gloves) and disposal of antineoplastics.18

Restricted Distribution

Available only through select specialty distributors.3 Contact manufacturer at 800-551-2231 or visit for ordering information.4

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

If a dose is missed or delayed, and the time between 2 sequential infusions is <6 weeks, administer pertuzumab 420 mg; do not wait until the next scheduled dose.1 If the time between 2 sequential infusions is ≥6 weeks, administer pertuzumab dose of 840 mg (i.e., same dose as initially used), followed by pertuzumab 420 mg every 3 weeks thereafter.1

Dosage Modification for Toxicity and Contraindications to Continued Therapy

Dosage reductions not recommended.1 If toxicities occur, reduce infusion rate or temporarily or permanently discontinue therapy based on causality.1

Monitor patients carefully until signs and symptoms have completely resolved.1

Left Ventricular Dysfunction

If left ventricular ejection fraction (LVEF) decreases to <40% or to 40–45% with an absolute decrease from baseline of ≥10%, withhold pertuzumab and trastuzumab for at least 3 weeks.1 (See Left Ventricular Dysfunction under Cautions.)

Reassess LVEF within approximately 3 weeks.1 If LVEF has recovered to >45% or to 40–45% with an absolute decrease from baseline of <10%, may resume pertuzumab therapy.1 If LVEF has not improved or has declined further, strongly consider discontinuing pertuzumab and trastuzumab, unless benefits outweigh risks.1

Consult prescribing information for docetaxel for detailed information on dosage modifications for this drug.1

Withhold or discontinue pertuzumab if trastuzumab is withheld or discontinued; however, if docetaxel is discontinued, may continue pertuzumab and trastuzumab therapy.1

Special Populations

Dosage adjustment not necessary based on body weight or baseline albumin concentration.1 (See Special Populations under Pharmacokinetics.)

Hepatic Impairment

No specific dosage recommendations at this time.1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Severe renal impairment (Clcr <30 mL/minute): No specific dosage recommendations at this time due to limited data.1 (See Renal Impairment under Cautions.)

Geriatric Patients

No specific dosage recommendations at this time.1 (See Geriatric Use under Cautions.)

Cautions for Pertuzumab

Contraindications

Manufacturer states none known.1

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.1 Embryotoxicity and fetotoxicity demonstrated in animals.1 Oligohydramnios, delayed fetal kidney development, and embryo-fetal death observed following administration of pertuzumab to pregnant cynomolgus monkeys at dosages producing concentrations 2.5–20 times that of human clinical exposure (based on peak plasma concentrations).1

Embryotoxic and fetotoxic effects likely to be present during all trimesters of pregnancy.1

Verify pregnancy status prior to initiation of pertuzumab.1 Advise women of childbearing potential to use effective contraceptive methods during and for 6 months after discontinuance of drug.1

If used during pregnancy or if patient becomes pregnant during therapy, apprise of potential fetal hazard.1 (See Pregnancy under Cautions.) Monitor for development of oligohydramnios in patients who become pregnant during therapy; perform appropriate fetal testing if oligohydramnios occurs.1 Efficacy of IV hydration in the management of oligohydramnios secondary to pertuzumab exposure unknown.1

Closely observe patients for 60 minutes after first infusion and for 30 minutes after subsequent infusions.1 If infusion or hypersensitivity reactions occur, may need to reduce infusion rate or temporarily or permanently discontinue therapy.1 (See Infusion or Hypersensitivity Reactions under Dosage and Administration.)

Other Warnings and Precautions

Left Ventricular Dysfunction

Decreases in LVEF reported with inhibitors of HER2, including pertuzumab.169 In principal efficacy study, pertuzumab not associated with increased incidence of symptomatic left ventricular systolic dysfunction (LVSD, congestive heart failure [CHF]) or decrease in LVEF compared with placebo.12 Median time to development of LVSD appears to be around cycle 4.6

Safety not established in patients with baseline LVEF ≤50%, prior history of CHF, decreases in LVEF to <50% during prior trastuzumab therapy, or conditions that could impair left ventricular function (e.g., uncontrolled hypertension, recent MI, serious cardiac arrhythmia requiring treatment, cumulative prior anthracycline exposure >360 mg/m2 of doxorubicin or its equivalent).1

Risk of LVSD possibly increased in patients who received prior anthracycline therapy or had prior radiation therapy to the chest area.1

Assess LVEF prior to initiation of therapy and at regular intervals (e.g., every 3 months) during treatment.1

If substantial decreases in LVEF occur, may need to temporarily or permanently discontinue therapy.1 (See Left Ventricular Dysfunction under Dosage and Administration.)

Evaluation of HER2

Assess breast tumors for HER2 overexpression prior to initiation of therapy because safety and efficacy of pertuzumab established only in patients with HER2-overexpressing tumors.1

In principal efficacy study, patients were required to have disease demonstrating an IHC score of 3+ or a FISH amplification ratio of ≥2.12 Limited data for patients with FISH-positive tumors that lack HER2 overexpression.1

Select laboratories with demonstrated proficiency in the specific technology being used; improper assay performance can lead to unreliable results.1

Specific Populations

Pregnancy

If used during pregnancy or if patient becomes pregnant while receiving therapy, apprise of potential fetal hazard.1 Encourage patient to enroll in the MotHER Pregnancy Registry (800-690-6720), and immediately notify Genentech Adverse Event Line (888-835-2555).1

Lactation

Not known whether pertuzumab is distributed into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

No overall differences in safety, efficacy, and pharmacokinetics relative to younger adults.1

Hepatic Impairment

Pharmacokinetics not studied in patients with hepatic impairment.1

Renal Impairment

Systemic exposure not altered by mild or moderate renal impairment; no dosage adjustment required.1 (See Renal Impairment under Dosage and Administration and also see Special Populations under Pharmacokinetics.)

Mild (Clcr of 60–90 mL/minute) or moderate (Clcr of 30–60 mL/minute) renal impairment: Systemic exposure is similar to that in patients with normal renal function.1 (See Renal Impairment under Dosage and Administration.)

Severe renal impairment (Clcr <30 mL/minute): Limited data.1

No relationship between Clcr and pertuzumab exposure observed over Clcr range of 27–244 mL/minute.1

Elimination

Half-life

Median half-life: 18 days.1

Stability

Storage

Parenteral

Injection

2–8°C in original carton to protect from light.1 Do not freeze or shake.1

Diluted solution: 2–8°C for up to 24 hours after dilution.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible1

Sodium chloride 0.9%

Incompatible1

Dextrose 5% in water

Actions

Binds specifically to extracellular dimerization domain (subdomain II) of HER2 protein, blocking heterodimerization of HER2 with other ligand-bound members of the HER family (i.e., epidermal growth factor receptor [EGFR]/HER1, HER3, HER4).123

Exhibits complementary mechanisms of action with trastuzumab; therefore, combined use with trastuzumab may result in more comprehensive inhibition of HER2 signaling.271317

Advice to Patients

Risk of fetal harm (e.g., embryo-fetal death, birth defects).1 Necessity of advising women of childbearing potential to use effective contraceptive methods during and for 6 months after discontinuance of drug.1 Encourage women who have been exposed to pertuzumab during pregnancy to enroll in the MotHER Pregnancy Registry by contacting 800-690-6720.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Importance of discontinuing breast-feeding during therapy.1

Risk of infusion or hypersensitivity reactions.1

Risk of decreased LVEF.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.